tbuckley/cabot-search huggingface dataset:
Blood Pressure and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction
Authors: Senthil Selvaraj, Muthiah Vaduganathan, Brian L. Claggett, Zi Michael Miao, James C. Fang, Orly Vardeny, Akshay S. Desai, Sanjiv J. Shah, Carolyn S.P. Lam, Felipe A. Martinez, Silvio E. Inzucchi, Rudolf A. de Boer, Magnus Petersson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon
Journal: JACC Heart Failure (2022)

Optimizing systolic blood pressure (SBP) in heart failure (HF) with preserved ejection fraction carries a Class I recommendation but with limited evidence. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have antihypertensive effects across cardiovascular disease.The authors examined the interplay between SBP and treatment effects of dapagliflozin on SBP and cardiovascular outcomes.The authors analyzed 6,263 DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) participants and related baseline and mean achieved SBP categories (<120, 120-129, 130-139, ≥140 mm Hg) to the primary outcome (cardiovascular death or worsening HF), secondary outcomes, and safety events. They analyzed whether the blood pressure-lowering effects of dapagliflozin accounted for its treatment effects by adjusting for the change in SBP from baseline to 1 month.The average age was 72 ± 10 years and 44% were women. SBP <120 mm Hg was associated with higher HF and mortality events, although amputation and stroke risk increased with higher SBP. Dapagliflozin reduced SBP by 1.8 (95% CI: 1.1-2.5) mm Hg compared with placebo at 1 month. The treatment effect of dapagliflozin on the primary outcome and Kansas City Cardiomyopathy Questionnaire total symptom score was consistent across SBP (interaction P = 0.15 and P = 0.98, respectively). Adverse events between arms were similar across SBP categories. The treatment effect was not accounted for by reducing blood pressure.In DELIVER, risk by SBP was augmented in the lowest and highest categories and varied by endpoint examined. Dapagliflozin modestly decreased SBP compared with placebo. Dapagliflozin was similarly efficacious and safe across the range of baseline SBP. The beneficial effects of dapagliflozin were not accounted for the changes in SBP. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
Reprogramming alveolar macrophage responses to TGF-β reveals CCR2+ monocyte activity that promotes bronchiolitis obliterans syndrome
Authors: Zhiyi Liu, Fuyi Liao, Jihong Zhu, Dequan Zhou, Gyu Seong Heo, Hannah P. Leuhmann, Davide Scozzi, Antanisha Parks, Ramsey Hachem, Derek E. Byers, Laneshia K. Tague, Hrishikesh S. Kulkarni, Marlene Cano, Brian W. Wong, Wenjun Li, Howard J. Haung, Alexander S. Krupnick, Daniel Kreisel, Yongjian Liu, Andrew E. Gelman
Journal: Journal of Clinical Investigation (2022)

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway TGF-β activity stimulated AMs to express CCL2, leading to CCR2+ monocyte-driven BOS development. Moreover, we found TGF-β receptor 2–dependent differentiation of CCR2+ monocytes was required for the generation of monocyte-derived AMs, which in turn promoted BOS by expanding tissue-resident memory CD8+ T cells that inflicted airway injury through Blimp-1–mediated granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-β–dependent network that couples CCR2+ monocyte recruitment and differentiation to alloimmunity and BOS.
Protein vaccine NVX-CoV2373 elicits functional T cell immunity
Authors: Pengcheng Zhou
Journal: Journal of Clinical Investigation (2022)

The SARS-CoV-2 vaccine NVX-CoV2373 is a protein-based vaccine that might circumvent the difficulties in distributing mRNA vaccines to regions with limited access to cold-chain and refrigeration. However, the NVX-CoV2373-induced T cell and antibody responses remain poorly understood. In this issue of the JCI, Moderbacher et al. characterized SARS-CoV-2-specific CD4+ and CD8+ T cell responses elicited by one or two doses of NVX-CoV2373 in individuals enrolled in a phase I/IIa trial. Substantially increased spike-specific CD4+ and T follicular helper cells were found after the first or second vaccine dose, with some individuals developing a modest spike-specific CD8+ T cell response. Correlation analysis revealed an association between spike-specific CD4+ T cells and neutralizing antibody titers. Notably, preexisting T cell immunity showed negligible effects on NVX-CoV2373-induced T cell responses. These findings indicate that the protein-based vaccine NVX-CoV2373 induces robust T cell immunity capable of recognizing SARS-CoV-2 antigens and supporting humoral immune responses.
TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons
Authors: Di Xie, Bernardo Stutz, Feng Li, Fan Chen, Haining Lv, Matija Sestan-Pesa, Jonatas Catarino, Jianlei Gu, Hongyu Zhao, Christopher E. Stoddard, Gordon G. Carmichael, Marya Shanabrough, Hugh S. Taylor, Zhong-Wu Liu, Xiao-Bing Gao, Tamas L. Horvath, Yingqun Huang
Journal: Journal of Clinical Investigation (2022)

The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.
GIGYF1-disturbed IGF-1R recycling: a potential contributor to autism spectrum disorder pathogenesis?
Authors: Mengen Xing, Qing Zhang, Weihong Song
Journal: Journal of Clinical Investigation (2022)

Autism spectrum disorder (ASD) is a highly variable and heritable neurodevelopmental disease (NDD) with strong genetic underpinnings. In this issue of the JCI, Chen et al. analyzed 2 previously reported, large-scale sequenced ASD cohorts and reported that GIGYF1 is the second most mutated among ASD risk genes. In this issue of the JCI, Chen et al. used a conditional mouse model combined with molecular technologies based on human genetic analyses to determine the critical role of GIGYF1 in ASD. GIGYF1-deficiency affected the recycling of IGF-1R, thereby suppressing the IGF-1R/ERK signaling pathway. Disruption of GIGYF1 in the developing mouse brain led to social deficits and cognitive impairments. These findings extend our understanding of ASD pathogenesis and provide an avenue for developing potentially effective preventions and treatments for patients with ASD.
Increased core body temperature exacerbates defective protein prenylation in mouse models of mevalonate kinase deficiency
Authors: Marcia A. Munoz, Oliver P. Skinner, Etienne Masle-Farquhar, Julie Jurczyluk, Ya Xiao, Emma K. Fletcher, Esther Kristianto, Mark P. Hodson, Seán I. O’Donoghue, Sandeep Kaur, Robert Brink, David G. Zahra, Elissa K. Deenick, Kristen A. Perry, Avril A.B. Robertson, Sam Mehr, Pravin Hissaria, Catharina M. Mulders-Manders, Anna Simon, Michael J. Rogers
Journal: Journal of Clinical Investigation (2022)

Mevalonate kinase deficiency (MKD) is characterized by recurrent fevers and flares of systemic inflammation, caused by biallelic loss-of-function mutations in MVK. The underlying disease mechanisms and triggers of inflammatory flares are poorly understood because of the lack of in vivo models. We describe genetically modified mice bearing the hypomorphic mutation p.Val377Ile (the commonest variant in patients with MKD) and amorphic, frameshift mutations in Mvk. Compound heterozygous mice recapitulated the characteristic biochemical phenotype of MKD, with increased plasma mevalonic acid and clear buildup of unprenylated GTPases in PBMCs, splenocytes, and bone marrow. The inflammatory response to LPS was enhanced in compound heterozygous mice and treatment with the NLRP3 inflammasome inhibitor MCC950 prevented the elevation of circulating IL-1β, thus identifying a potential inflammasome target for future therapeutic approaches. Furthermore, lines of mice with a range of deficiencies in mevalonate kinase and abnormal prenylation mirrored the genotype-phenotype relationship in human MKD. Importantly, these mice allowed the determination of a threshold level of residual enzyme activity, below which protein prenylation is impaired. Elevated temperature dramatically but reversibly exacerbated the deficit in the mevalonate pathway and the defective prenylation in vitro and in vivo, highlighting increased body temperature as a likely trigger of inflammatory flares.
Parental genomes segregate into distinct blastomeres during multipolar zygotic divisions leading to mixoploid and chimeric blastocysts
Authors: Tine De Coster, Heleen Masset, Olga Tšuiko, Maaike Catteeuw, Yan Zhao, Nicolas Dierckxsens, Ainhoa Larreategui Aparicio, Eftychia Dimitriadou, Sophie Debrock, Karen Peeraer, Marta de Ruijter-Villani, Katrien Smits, Ann Van Soom, Joris Robert Vermeesch
Journal: Genome biology (2022)

During normal zygotic division, two haploid parental genomes replicate, unite and segregate into two biparental diploid blastomeres.
Harnessing tumorous flaws for immune supremacy: is miRNA-155 the weak link in breast cancer progression?
Authors: Samantha Sharma, Mateusz Opyrchal, Xiongbin Lu
Journal: Journal of Clinical Investigation (2022)

With the advent of immune checkpoint blockade (ICB) therapy, treatment strategies for late-stage cancers have seen a radical advancement. In this issue of the JCI, Wang et al. characterize the functional role of miR-155 in breast cancer and its potential in harnessing the efficacy of immunotherapy. The study reports that high expression levels of miR-155 in breast cancer cells downregulated suppressor of cytokine signaling 1 (SOCS1), increased the phosphorylated STAT1 (pSTAT1)/pSTAT3 ratio, and thereby stimulated chemoattractants for tumor infiltration of effector T cells. Moreover, miR-155 overexpression set the stage for ICB therapy via increased programmed death ligand 1 (PD-L1) expression on cancer cells and enhanced immunological memory response via the release of miR-155-containing extracellular vesicles. Collectively, these data suggest that miR-155 is a strong candidate as a prognostic biomarker for ICB therapy.
Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder
Authors: Layla Thurston, Tia Hunjan, Edouard G. Mills, Matthew B. Wall, Natalie Ertl, Maria Phylactou, Beatrice Muzi, Bijal Patel, Emma C. Alexander, Sofiya Suladze, Manish Modi, Pei C. Eng, Paul A. Bassett, Ali Abbara, David Goldmeier, Alexander N. Comninos, Waljit S. Dhillo
Journal: Journal of Clinical Investigation (2022)

BACKGROUNDHypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODSUsing psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTSMC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSIONThese data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATIONClinicalTrials.gov NCT04179734.FUNDINGThis is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (CS-2018-18-ST2-002 and RP-2014-05-001).
Atrioventricular Junctional Rhythm in Patients Receiving Oral Verapamil Therapy
Authors: W. Scott Walker
Journal: JAMA (1983)

Six patients had frequent episodes of atrioventricular junctional rhythm during long-term oral verapamil therapy. In no instance was this rhythm associated with symptoms or adverse effects, nor did it force a discontinuation of therapy or a reduction in verapamil dosage. In the patient receiving oral verapamil therapy, atrioventricular junctional rhythm should not be considered a manifestation of drug toxicity. (<i>JAMA</i>1983;249:389-390)
Practical Gynecology. A Comprehensive Text-Book for Students and Physicians.
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Study of Various Tests to Detect Asymptomatic Urinary Tract Infections in an Obstetric Population
Authors: John W. Bachman
Journal: JAMA (1993)

<h3>Objective.</h3> —To compare rapid screening techniques for detecting asymptomatic urinary tract infections (AUTIs) in pregnant women. <h3>Design.</h3> —Comparison of results of the screening tests of urinalysis, urine dipstick, and Gram's staining with the results of standard urine culture at an initial prenatal visit. In follow-up visits, urine dipstick testing was compared with urinalysis. <h3>Setting.</h3> —Departments of Family Medicine and Obstetrics and Gynecology, Mayo Clinic, Rochester, Minn. <h3>Patients.</h3> —Pregnant women (1047) from the local community were screened for AUTI on initial and follow-up visits. <h3>Methods.</h3> —Initial prenatal urine was tested by using urine dipstick testing, urinalysis, Gram's staining, and urine culture. At each follow-up visit, urine specimens were tested by using urine dipstick and urinalysis. <h3>Main Outcome Measures.</h3> —Sensitivity and specificity, incremental patient costs, and clinical outcomes were used to assess the effectiveness of the techniques. <h3>Results.</h3> —On initial visits, rapid screening tests for AUTI in pregnant women revealed the following: Gram's staining identified 22 of 24 patients with AUTI (sensitivity, 91.7%; specificity, 89.2%); urine dipstick, 12 of 24 (sensitivity, 50.0%; specificity, 96.9%); and urinalysis with presence of leukocytes, six of 24 (sensitivity, 25.0%; specificity, 99.0%). In follow-up visits, urine dipstick tests detected 19 infections and urinalysis, three (positive predictive value, 5% compared with 3%). <h3>Conclusions.</h3> —Urine dipstick testing for nitrites identified half of all patients with urinary tract infections and was superior to urinalysis on follow-up visits. Although Gram's staining is more expensive, it was more accurate for AUTI than urinalysis or urine dipstick test for nitrites. Urinalysis was never the test of choice because it was more expensive and detected fewer positive cultures. Leukocyte measurement correlated poorly with AUTI. (<i>JAMA</i>. 1993;270:1971-1974)
Treating Depression in Medical Conditions May Improve Quality of Life
Authors: Lynne Lamberg
Journal: JAMA (1996)

DEPRESSION is common in medical illness: it is both a physiologic consequence of the illness and a psychological reaction to it. It also may be a side effect of some drug therapies. In all instances, aggressive treatment of the depression may promote better compliance with general medical care and lower its cost, improve the patient's quality of life, and possibly forestall suicide, according to speakers in several sessions at the annual meeting of the American Psychiatric Association (APA) in New York City. Depressive disorders occur in an estimated 6% of the general population. For those with medical illnesses, the prevalence may soar past 50%, said speakers who focused on the practical implications for primary care clinicians. <h3>Neurologic Illness</h3> Within a week of experiencing a stroke, said Stuart Yudofsky, MD, professor and chair of the Department of Psychiatry at Baylor College of Medicine, Houston, Tex, more than half the patients meet
Ten Years of Operative Surgery in the Provinces
Authors: A. Prichard
Journal: BMJ (1861)

without the aid of a bootjack, that the patient had almost fainted away.Mercurial and other purgative medicines, but especially a hot bath every night on going to bed, at 1030, for fifteen minutes, were the most effectual remedies.Fomentations did good.There was a disposition to an early morning exacerbation.The jar of a carriage was intolerable.This neuritic sciatica is of an essentiallv different character from any muscular rheumatism, as lumbago.As the latter is inflammation of the muscular fibre, the former is most distinctly, in its twofold set of symptoms, a neuritis.The numbness is similar to that experienced in the second stage of odontalgia, doubtless from hypernemia of the neurilemma and compression of the nervous sub.stance."Romberg, stating the diagnosis of sciatica, says: 4' Until very recently, pain confined to the trunk of the
Choriocarcinoma in Ibadan, Nigeria: Epidemiologic Aspects&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1974)

Choriocarcinoma, the third most common malignant tumor in Nigerian females, is more frequent than malignant ovarian neoplasms but less frequent than cervical and breast cancer. It was diagnosed in 66% of 285 histologic materials registered as malignant trophoblastic disease. Its ratio frequency in our Cancer Registry over a 12-year period was 2.2%. Choriocarcinoma had a necropsy ratio of 1∶89 and peak age frequency in the third or fourth decades of life. The uterus was the most common site of the primary growth, and hematogenous metastases were widespread. An increased aggregation of mononuclear cells around the tumor was observed.
The 'Growth Disease' in American Institutional Medicine
Authors: Albert J. Miller
Journal: JAMA (1982)

THE MEDICAL system has become huge, having followed an explosive industrial-type growth pattern. Hospitals and medical centers have been oriented to expansion, and medical administrators—both lay and physician—have been bred according to the growth concept. The rule has been that growth equals progress and, hence, success. Hospital leaders are loath to give up this measure of achievement, which they have learned from industry, although it is a concept that leads to great costs in money and efficiency and that runs contrary to our social needs. The growth-oriented administrators of our medical institutions are generally supported by strikingly passive governing boards, almost always consisting predominantly of businessmen, who casually provide their legal authority and psychological support to the administration. The resultant growth includes more buildings, more facilities, larger staff, more support personnel, more administrators, and more power concentrated in a central administrative office. Ironically, the boards of these institutions allow the
Studies on Chromosomes of Three Human Cell Lines Harboring the EB Virus Particles&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Yoshinori Kurita, Toyoro Osato, Yohei Ito
Journal: JNCI Journal of the National Cancer Institute (1968)

Chromosomes were studied of 3 human cell lines known to harbor the EB virus: THE-2 and THE-3, derived from human embryo cells exposed to culture fluids of human leukemic cells in vitro, and P3 (Jiyoye) and its subline, P3HR-1, derived from Burkitt's lymphoma. THE-2 cells were pseudodiploid and female, whereas THE-3, P3, and P3HR-1 cells were hyperdiploid and male. These 3 cell lines and the 1 subline had some common chromosome anomalies: a) an extra chromosome in group 6–12 + X, probably a #10 chromosome, in all lines; b) a prominent subterminal secondary constriction in the #10 chromosome in all lines; and c) one metacentric marker chromosome of the size of the #10 chromosome, morphologically identical to that reported in some Burkitt lymphoma cell lines, consistently present in THE-3, P3, and P3HR-1 cell lines. The close relation of chromosomes of THE-2 and THE-3 cell lines to those of Burkitt lymphoma cell lines and some implications of the #10 chromosome lesion in human cell lines harboring EB virus particles are discussed.
CYCLOSPORIN, URIC ACID, AND THE KIDNEY
Authors: J.M. Griño, I. Sabater, A.M. Castelao, J. Torras, J. Alsina, K.M.L. Leunissen, F. Bosman, J.P.Van Hooff, K. Farrington, Z. Varghese, M. Raftery, O.N. Fernando, P. Sweny, J.F. Moorhead
Journal: The Lancet (1985)